title: "Dynamic range" of inferred phenotypic HIV drug resistance values in clinical practice.
abstract: BACKGROUND
  'Virtual' or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values.
  
  
  METHODS
  All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the "dynamic range" (defined here by the 10th and 90th percentiles for fold-change in IC₅₀ amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort.
  
  
  RESULTS
  The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC₅₀ of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small "dynamic ranges" with values of <4-fold change observed in > 99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges.
  
  
  CONCLUSIONS
  We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Luke C
authors.initials: LC
authors.lastname: Swenson
authors.forename: Graham
authors.initials: G
authors.lastname: Pollock
authors.forename: Brian
authors.initials: B
authors.lastname: Wynhoven
authors.forename: Theresa
authors.initials: T
authors.lastname: Mo
authors.forename: Winnie
authors.initials: W
authors.lastname: Dong
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005500:Follow-Up Studies; D005544:Forecasting; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D017711:Nonlinear Dynamics; D010641:Phenotype; D010818:Practice Patterns, Physicians'; D011364:Professional Practice; D011379:Prognosis; D017211:Treatment Failure; D019562:Viral Load / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents